The specific aims are to: 1) Assess the role of the gp39/CD40 interaction in the induction of intrathymic clonal deletion by superantigens in normal mice or by peptide antigens in TCR transgenic mice. Attempts will be made to identify the critical CD40+ cell in this system. 2) Assess the role of the gp39/CD40 interaction in the induction of peripheral tolerance by B-cells. Studies will be aimed at determining the cellular basis for this phenomenon using conventional and TCR transgenic mice. 3) Determine how blockage of the gp39/CD40 interaction prevents EAE. Attempts will be made to determine if macrophage functions are affected or if T-cell tolerance is induced.